Evidence for mood instability in patients with bipolar disorder: Applying multilevel hidden Markov modeling to intensive longitudinal ecological momentary assessment data.

Bipolar disorder (BD) is a chronic psychiatric condition characterized by large episodic changes in mood and energy. Recently, BD has been proposed to be conceptualized as chronic cyclical mood instability, as opposed to the traditional view of alternating discrete episodes with stable periods in-between. Recognizing this mood instability may improve care and call for high-frequency measures coupled with advanced statistical models. To uncover empirically derived mood states, a multilevel hidden Markov model (HMM) was applied to 4-month ecological momentary assessment data in 20 patients with BD, yielding ∼9,820 assessments in total. Ecological momentary assessment data comprised self-report questionnaires (5 × daily) measuring manic and depressive constructs. Manic and depressive symptoms were also assessed weekly using the Altman Self-Rating Mania Scale and the Quick Inventory for Depressive Symptomatology Self-Report. Alignment between HMM-uncovered momentary mood states and weekly questionnaires was assessed with a multilevel linear model. HMM uncovered four mood states: neutral, elevated, mixed, and lowered, which aligned with weekly symptom scores. On average, patients remained < 25 hr in one state. In almost half of the patients, mood instability was observed. Switching between mood states, three patterns were identified: patients switching predominantly between (a) neutral and lowered states, (b) neutral and elevated states, and (c) mixed, elevated, and lowered states. In all, elevated and lowered mood states were interspersed by mixed states. The results indicate that chronic mood instability is a key feature of BD, even in "relatively" euthymic periods. This should be considered in theoretical and clinical conceptualizations of the disorder. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Shaping tomorrow's support: baseline clinical characteristics predict later social functioning and quality of life in schizophrenia spectrum disorder.

PURPOSE: We aimed to explore the multidimensional nature of social inclusion (mSI) among patients diagnosed with schizophrenia spectrum disorder (SSD), and to identify the predictors of 3-year mSI and the mSI prediction using traditional and data-driven approaches. METHODS: We used the baseline and 3-year follow-up data of 1119 patients from the Genetic Risk and Outcome in Psychosis (GROUP) cohort in the Netherlands. The outcome mSI was defined as clusters derived from combined analyses of thirteen subscales from the Social Functioning Scale and the brief version of World Health Organization Quality of Life questionnaires through K-means clustering. Prediction models were built through multinomial logistic regression (ModelMLR) and random forest (ModelRF), internally validated via bootstrapping and compared by accuracy and the discriminability of mSI subgroups. RESULTS: We identified five mSI subgroups: "very low (social functioning)/very low (quality of life)" (8.58%), "low/low" (12.87%), "high/low" (49.24%), "medium/high" (18.05%), and "high/high" (11.26%). The mSI was robustly predicted by a genetic predisposition for SSD, premorbid adjustment, positive, negative, and depressive symptoms, number of met needs, and baseline satisfaction with the environment and social life. The ModelRF (61.61% [54.90%, 68.01%]; P =0.013) was cautiously considered outperform the ModelMLR (59.16% [55.75%, 62.58%]; P =0.994). CONCLUSION: We introduced and distinguished meaningful subgroups of mSI, which were modestly predictable from baseline clinical characteristics. A possibility for early prediction of mSI at the clinical stage may unlock the potential for faster and more impactful social support that is specifically tailored to the unique characteristics of the mSI subgroup to which a given patient belongs.

Moving from supported to independent living: what are the barriers and facilitators for individuals with psychosis?

PURPOSE: Living independently, as opposed to in sheltered housing or with caregivers, is an important aim in the recovery of individuals with psychosis, but the transition to independence can be challenging. This study aims to investigate how individuals with psychosis move between living arrangements and to identify the barriers and facilitators of moving towards independence. METHODS: The living arrangements of 1119 individuals with non-affective psychosis from the Genetic Risk and Outcome of Psychosis study were assessed at baseline, at three- and six-year follow-ups and further categorized as either supported (sheltered housing or with parents) or independent (single or with partner/family). We estimated the probabilities of transitioning between the living statuses and investigated the influence of demographic characteristics, symptomatology, cognition, social support, and premorbid social adjustment on transition using Markov chain modelling. RESULTS: The majority of individuals living in supported housing remained there during the six-year follow-up period (~ 60%). The likelihood of moving from supported to independent living was twice as high for participants who were younger, five-to-six times higher for women, twice as high for individuals with better overall cognition, and five times higher for those with a course of low positive symptoms. CONCLUSION: This study highlights that a large group of individuals with psychosis in supported housing is unlikely to move to independent living. Older men with cognitive impairments and who show continuous severe positive symptoms are the least likely to move living independently. Tailored interventions for these at-risk individuals could increase their chances of moving to independent living.

Association of clinical symptoms and cardiometabolic dysregulations in patients with schizophrenia spectrum disorders.

BACKGROUND: Patients with schizophrenia spectrum disorders (SSD) have a shortened life expectancy related to cardiovascular diseases. We investigated the association of cognitive, positive, and negative symptoms with cardiometabolic dysregulations in SSD patients. METHODS: Overall, 1,119 patients from the Genetic Risk and Outcome in Psychosis (GROUP) study were included. Cognitive function, positive and negative symptoms were assessed at baseline, 3-year, and 6-year. Cardiometabolic biomarkers were measured at 3-year follow-up. We used linear and multinomial logistic regression models to test the association between cardiometabolic biomarkers and clinical trajectories and performed mediation analyzes, while adjusting for clinical and demographic confounders. RESULTS: Cognitive performance was inversely associated with increased body mass index (mean difference [ß], ßhigh = -1.24, 95% CI = -2.28 to 0.20, P = 0.02) and systolic blood pressure (ßmild = 2.74, 95% CI = 0.11 to 5.37, P = 0.04). The severity of positive symptoms was associated with increased glycated hemoglobin (HbA1c) levels (ßlow = -2.01, 95% CI = -3.21 to -0.82, P = 0.001). Increased diastolic blood pressure (ORhigh-decreased = 1.04, 95% CI = 1.01 to 1.08, P = 0.02; ORhigh-increased = 1.04, 95% CI = 1.00 to 1.08, P = 0.048) and decreased high-density lipoprotein (OR high-increased = 6.25, 95% CI = 1.81 to 21.59, P = 0.004) were associated with more severe negative symptoms. Increased HbA1c (ORmoderate = 1.05, 95% CI = 1.01 to 1.10, P = 0.024; ORhigh = 1.08, 95% CI = 1.02 to 1.14, P = 0.006) was associated with more severe positive symptoms. These associations were not mediated by antipsychotics. CONCLUSIONS: We showed an association between cardiometabolic dysregulations and clinical and cognitive symptoms in SSD patients. The observed associations underscore the need for early identification of patients at risk of cardiometabolic outcomes.

Life years lost for users of specialized mental healthcare.

BACKGROUND: Mental disorders are burdensome and are associated with increased mortality. Mortality has been researched for various mental disorders, especially in countries with national registries, including the Nordic countries. Yet, knowledge gaps exist around national differences, while also relatively less studies compare mortality of those seeking help for mental disorders in specialized mental healthcare (SMH) by diagnosis. Additional insight into such mortality distributions for SMH users would be beneficial for both policy and research purposes. We aim to describe and compare the mortality in a population of SMH users with the mortality of the general population. Additionally, we aim to investigate mortality differences between sexes and major diagnosis categories: anxiety, depression, schizophrenia spectrum and other psychotic disorders, and bipolar disorder. METHODS: Mortality and basic demographics were available for a population of N = 10,914 SMH users in the north of The Netherlands from 2010 until 2017. To estimate mortality over the adult lifespan, parametric Gompertz distributions were fitted on observed mortality using interval regression. Life years lost were computed by calculating the difference between integrals of the survival functions for the general population and the study sample, thus correcting for age. Survival for the general population was obtained from Statistics Netherlands (CBS). RESULTS: SMH users were estimated to lose 9.5 life years (95% CI: 9.4-9.6). Every major diagnosis category was associated with a significant loss of life years, ranging from 7.2 (95% CI: 6.4-7.9) years for anxiety patients to 11.7 (95% CI: 11.0-12.5) years for bipolar disorder patients. Significant differences in mortality were observed between male SMH users and female SMH users, with men losing relatively more life years: 11.0 (95% CI: 10.9-11.2) versus 8.3 (95% CI: 8.2-8.4) respectively. This difference was also observed between sexes within every diagnosis, although the difference was insignificant for bipolar disorder. CONCLUSION: There were significant differences in mortality between SMH users and the general population. Substantial differences were observed between sexes and between diagnoses. Additional attention is required, and possibly specific interventions are needed to reduce the amount of life years lost by SMH users.

Pharmacogenetics of Long-Term Outcomes of Schizophrenia Spectrum Disorders: The Functional Role of CYP2D6 and CYP2C19.

Schizophrenia spectrum disorders (SSD) are complex mental disorders, and while treatment with antipsychotics is important, many patients do not respond or develop serious side effects. Genetic variation has been shown to play a considerable role in determining an individual's response to antipsychotic medication. However, previous pharmacogenetic (PGx) studies have been limited by small sample sizes, lack of consensus regarding relevant genetic variants, and cross-sectional designs. The current study aimed to investigate the association between PGx variants and long-term clinical outcomes in 691 patients of European ancestry with SSD. Using evidence from the literature on candidate genes involved in antipsychotic pharmacodynamics, we created a polygenic risk score (PRS) to investigate its association with clinical outcomes. We also created PRS using core variants of psychotropic drug metabolism enzymes CYP2D6 and CYP2C19. Furthermore, the CYP2D6 and CYP2C19 functional activity scores were calculated to determine the relationship between metabolism and clinical outcomes. We found no association for PGx PRSs and clinical outcomes; however, an association was found with CYP2D6 activity scores by the traditional method. Higher CYP2D6 metabolism was associated with high positive and high cognitive impairment groups relative to low symptom severity groups. These findings highlight the need to test PGx efficacy with different symptom domains. More evidence is needed before pharmacogenetic variation can contribute to personalized treatment plans.

MicroRNAs and pro-inflammatory cytokines as candidate biomarkers for recent-onset psychosis.

BACKGROUND: Recent studies on the schizophrenia spectrum and other psychotic disorders showed that alternation of immune system components, particularly microRNAs (miRNAs) and pro-inflammatory compounds, plays a significant role in developing the illness. The study aimed to evaluate serum expression of the miRNA-26a, miRNA-106a, and miRNA-125b as genetic factors and serum levels of IL-6, IL-1ß, and TNF-α as pro-inflammatory factors in an IranianAzeri population. METHODS: Forty patients with recent-onset non-affective psychosis and 40 healthy people as a control group were involved. Expression levels of miRNAs and serum levels of the cytokines were measured using RT-qPCR and ELISA, respectively. T-test, receiver operating characteristics (ROC), and spearman correlation coefficient were carried out data analysis. RESULTS: Findings showed higher levels of IL-6, IL-1ß, TNF-α, miR-26a, and miR-106a in the plasma of the patients' group compared with the control. miRNA-26a showed a statistically significant higher level (p < .003) compared to the control group, with AUC = 0.84 (95% CI: 0.77 to 0.93, P < .001) and cut-off point = 0.17 in comparison to other miRNAs as mentioned above; in this regard, it might be a suggestive biomarker for schizophrenia in the early stage of the illness. Moreover, miRNAs' expression level was not substantially associated with the level of any measured cytokines above. CONCLUSIONS: miR-26a might be a suggestive biomarker for schizophrenia in the early stage of the illness. Given that the relationship between other miRNAs and cytokines is not yet well understood; accordingly, there are encouragement and support for continued research in this fascinating field.

Deep Clinical Phenotyping of Schizophrenia Spectrum Disorders Using Data-Driven Methods: Marching towards Precision Psychiatry.

Heterogeneity is the main challenge in the traditional classification of mental disorders, including schizophrenia spectrum disorders (SSD). This can be partly attributed to the absence of objective diagnostic criteria and the multidimensional nature of symptoms and their associated factors. This article provides an overview of findings from the Genetic Risk and Outcome of Psychosis (GROUP) cohort study on the deep clinical phenotyping of schizophrenia spectrum disorders targeting positive and negative symptoms, cognitive impairments and psychosocial functioning. Three to four latent subtypes of positive and negative symptoms were identified in patients, siblings and controls, whereas four to six latent cognitive subtypes were identified. Five latent subtypes of psychosocial function-multidimensional social inclusion and premorbid adjustment-were also identified in patients. We discovered that the identified subtypes had mixed profiles and exhibited stable, deteriorating, relapsing and ameliorating longitudinal courses over time. Baseline positive and negative symptoms, premorbid adjustment, psychotic-like experiences, health-related quality of life and PRSSCZ were found to be the strong predictors of the identified subtypes. Our findings are comprehensive, novel and of clinical interest for precisely identifying high-risk population groups, patients with good or poor disease prognosis and the selection of optimal intervention, ultimately fostering precision psychiatry by tackling diagnostic and treatment selection challenges pertaining to heterogeneity.

Six-year trajectories and associated factors of positive and negative symptoms in schizophrenia patients, siblings, and controls: Genetic Risk and Outcome of Psychosis (GROUP) study.

Positive and negative symptoms are prominent but heterogeneous characteristics of schizophrenia spectrum disorder (SSD). Within the framework of the Genetic Risk and Outcome of Psychosis (GROUP) longitudinal cohort study, we aimed to distinguish and identify the genetic and non-genetics predictors of homogenous subgroups of the long-term course of positive and negative symptoms in SSD patients (n = 1119) and their unaffected siblings (n = 1059) in comparison to controls (n = 586). Data were collected at baseline, and after 3- and 6-year follow-ups. Group-based trajectory modeling was applied to identify latent subgroups using positive and negative symptoms or schizotypy scores. A multinomial random-effects logistic regression model was used to identify predictors of latent subgroups. Patients had decreasing, increasing, and relapsing symptoms course. Unaffected siblings and healthy controls had three to four subgroups characterized by stable, decreasing, or increasing schizotypy. PRSSCZ did not predict the latent subgroups. Baseline symptoms severity in patients, premorbid adjustment, depressive symptoms, and quality of life in siblings predicted long-term trajectories while were nonsignificant in controls. In conclusion, up to four homogenous latent subgroups of symptom course can be distinguished within patients, siblings, and controls, while non-genetic factors are the main factors associated with the latent subgroups.

Values and practice of collaboration in a mental health care system in the Netherlands: a qualitative study.

BACKGROUND: To offer optimal care, the mental health system needs new routes for collaboration, involving both interprofessional and interorganizational aspects. The transition from intramural to extramural mental health care has given rise to new dynamics between public and mental health care, introducing a challenge for interprofessional and interorganizational collaboration. This study aims to determine values and expectations of collaboration and to understand how collaboration in mental health care organizations takes shape in daily practice. METHODS: We conducted a qualitative study using semi-structured interviews and a focus group, in the setting of the Program for Mentally Vulnerable Persons (PMV). Data were analysed following thematic analysis. RESULTS: We found three aspect that were considered important in collaboration: commonality, relationships, and psychological ownership. However, our findings indicate a discrepancy between what is considered essential in collaboration and how this materializes in day-to-day practice: collaboration appears to be less manageable than anticipated by interviewees. Our data suggest psychological ownership should be added as value to the interorganizational collaboration theory. CONCLUSION: Our study offers a new definition of collaboration and adding "psychological ownership" to the existing literature on collaboration theory. Furthermore, we gained insight into how collaboration between different organizations works in practice. Our research points to a discrepancy between what all the partners find important in collaboration, and what they actually do in practice. Finally, we expressed ways to improve the collaboration, such as choosing between a chain or a network approach and acting on it and re-highlighting the goal of the Program Mentally Vulnerable persons.

Age-Related Social Cognitive Performance in Individuals With Psychotic Disorders and Their First-Degree Relatives.

BACKGROUND: Social cognitive impairment is a recognized feature of psychotic disorders. However, potential age-related differences in social cognitive impairment have rarely been studied. STUDY DESIGN: Data came from 905 individuals with a psychotic disorder, 966 unaffected siblings, and 544 never-psychotic controls aged 18-55 who participated in the Genetic Risk and Outcome of Psychosis (GROUP) study. Multilevel linear models were fitted to study group main effects and the interaction between group and age on emotion perception and processing (EPP; degraded facial affect recognition) and theory of mind (ToM; hinting task) performance. Age-related differences in the association between socio-demographic and clinical factors, and EPP and ToM were also explored. STUDY RESULTS: Across groups, EPP performance was associated with age (ß = -0.02, z = -7.60, 95% CI: -0.02, -0.01, P < .001), with older participants performing worse than younger ones. A significant group-by-age interaction on ToM (X2(2) = 13.15, P = .001) indicated that older patients performed better than younger ones, while no age-related difference in performance was apparent among siblings and controls. In patients, the association between negative symptoms and ToM was stronger for younger than older patients (z = 2.16, P = .03). CONCLUSIONS: The findings point to different age-related performance patterns on tests of 2 key social cognitive domains. ToM performance was better in older individuals, although this effect was only observed for patients. EPP was less accurate in older compared with younger individuals. These findings have implications with respect to when social cognitive training should be offered to patients.

Understanding Lifelong Factors and Prediction Models of Social Functioning After Psychosis Onset Using the Large-Scale GROUP Cohort Study.

BACKGROUND AND HYPOTHESIS: Current rates of poor social functioning (SF) in people with psychosis history reach 80% worldwide. We aimed to identify a core set of lifelong predictors and build prediction models of SF after psychosis onset. STUDY DESIGN: We utilized data of 1119 patients from the Genetic Risk and Outcome in Psychosis (GROUP) longitudinal Dutch cohort. First, we applied group-based trajectory modeling to identify premorbid adjustment trajectories. We further investigated the association between the premorbid adjustment trajectories, six-year-long cognitive deficits, positive, and negative symptoms trajectories, and SF at 3-year and 6-year follow-ups. Next, we checked associations between demographics, clinical, and environmental factors measured at the baseline and SF at follow-up. Finally, we built and internally validated 2 predictive models of SF. STUDY RESULTS: We found all trajectories were significantly associated with SF (P < .01), explaining up to 16% of SF variation (R2 0.15 for 3- and 0.16 for 6-year follow-up). Demographics (sex, ethnicity, age, education), clinical parameters (genetic predisposition, illness duration, psychotic episodes, cannabis use), and environment (childhood trauma, number of moves, marriage, employment, urbanicity, unmet needs of social support) were also significantly associated with SF. After validation, final prediction models explained a variance up to 27% (95% CI: 0.23, 0.30) at 3-year and 26% (95% CI: 0.22, 0.31) at 6-year follow-up. CONCLUSIONS: We found a core set of lifelong predictors of SF. Yet, the performance of our prediction models was moderate.

Personal recovery suits us all: A study in patients with non-affective psychosis, unaffected siblings and healthy controls.

Personal recovery transcends illness and is a unifying human experience. Core elements in personal recovery are hope, meaning, and rebuilding oneself. Here we aim to investigate whether factors associated with personal recovery in patients with non-affective psychosis, unaffected siblings and healthy controls are similar. We investigated the association between personal recovery and resilience, social support, socio-demographic and illness-related variables in 580 patients, 630 siblings, and 351 healthy controls who participated in the Genetic Risk and Outcome of Psychosis (GROUP) study. Bi-variate associations between personal recovery and individual variables were assessed and multiple linear regression analyses were performed to estimate the proportion of variance in personal recovery that could be accounted for by the predictors and to investigate which predictors independently added to the model. Positive self was significantly and independently associated with personal recovery in all three groups. Pro-active action taking also seems to be important. Social functioning significantly contributed to explained variance in patients and siblings. Regarding illness-related factors, depressive symptoms had impact on personal recovery in both patients and siblings, whereas positive symptoms only did in siblings. The findings imply that not only personal recovery itself, but also some associated factors are universally human and suit us all. This means that patients and non-patients share supportive factors of personal recovery which may help to reach mutual understanding. Recovery-oriented practices and mental health services might be more effective when focusing also on improving self-image, functional coping styles and generating social interaction, next to the reduction of affective symptoms.

Visual Hallucinations in Psychosis: The Curious Absence of the Primary Visual Cortex.

BACKGROUND AND HYPOTHESIS: Approximately one-third of patients with a psychotic disorder experience visual hallucinations (VH). While new, more targeted treatment options are warranted, the pathophysiology of VH remains largely unknown. Previous studies hypothesized that VH result from impaired functioning of the vision-related networks and impaired interaction between those networks, including a possible functional disconnection between the primary visual cortex (V1) and higher-order visual processing regions. Testing these hypotheses requires sufficient data on brain activation during actual VH, but such data are extremely scarce. STUDY DESIGN: We therefore recruited seven participants with a psychotic disorder who were scanned in a 3 T fMRI scanner while indicating the occurrence of VH by pressing a button. Following the scan session, we interviewed participants about the VH experienced during scanning. We then used the fMRI scans to identify regions with increased or decreased activity during VH periods versus baseline (no VH). STUDY RESULTS: In six participants, V1 was not activated during VH, and in one participant V1 showed decreased activation. All participants reported complex VH such as human-like beings, objects and/or animals, during which higher-order visual areas and regions belonging to the vision-related networks on attention and memory were activated. DISCUSSION: These results indicate that VH are associated with diffuse involvement of the vision-related networks, with the exception of V1. We therefore propose a model for the pathophysiology of psychotic VH in which a dissociation of higher-order visual processing areas from V1 biases conscious perception away from reality and towards internally generated percepts.

ARAS recent onset acute phase psychosis survey, a prospective observational cohort of first episode psychosis in Iran-the cohort profile.

The Middle East is underrepresented in psychosis research. The ARAS recent onset acute phase psychosis survey (ARAS) is a longitudinal cohort across multiple centers in Iran, established to investigate characteristics, determinants and early course of psychosis in a non-Western, Middle East context. Here, baseline characteristics of the ARAS cohort are reported. The ARAS cohort enrolled patients with recent onset psychosis from September 2018 to September 2021 in East Azerbaijan, Kermanshah and Tehran, including Iranian patients from different sociocultural contexts. The baseline assessment included demographics, socioeconomic status, clinical (positive, negative, depressive symptoms) and psychosocial (religiosity, social support, self-stigma) characteristics, cognitive functioning, metabolic profile, substance use and medication use measured by validated questionnaires. These assessments will be followed up after one and five years. A total of 500 patients with a first episode of psychosis were enrolled from three provinces in Iran. With 74.1% being male, the mean age (SD) of patients was 32.3 (9.7) years. Nearly a quarter of patients was diagnosed with schizophrenia and 36.8% with substance induced psychotic disorder. Amphetamine (24%) and opium (12%) use were common, cannabis use was not (5%). Only 6.1% of patients lived alone while 29% of patients was married and had children. The majority of them had achieved secondary educational level and 34% had a paid job. The most common antipsychotic treatment was risperidone. There was a wide range for scores of PANSS, with 9.4% having dominant negative symptoms. The most common prescribed medication was risperidone. Near to 40% of patients had noticeable signs of depression and prevalence of metabolic syndrome was 13.4%. The majority of patients (57.2%) had moderate and 5.4% reported to have severe disability. More than 30% reported to be highly religious. Patients had the highest satisfaction with people living with, and the lowest for finance and job.

Long-term treatment of antipsychotics and combined therapy with other psychotropic medications inducing weight gain in patients with non-affective psychotic disorder: Evidence from GROUP, a longitudinal study.

INTRODUCTION: Antipsychotics (APs) can cause weight gain. Little is known about changes in weight when APs are combined with other psychotropics. This study examines the weight change in patients undergoing long-term treatment with APs or with AP combined with other psychotropics. METHODS: Patients with non-affective psychotic disorder from the GROUP study were divided into three groups: AP medication group (APm) (n = 100), AP in combination with other psychotropics (APc) (n = 73), and medication-free (Meds-free) (n = 100). Weight change was examined at inclusion and after three years using a paired-sample t-test. An Independent-sample t-test was performed to evaluate weight change among patients taking clozapine, olanzapine, and quetiapine and individuals not taking these medications. Linear regression was performed to evaluate the association between covariates and weight. RESULTS: Patients in the APm group [mean = 1.800 kg, t(99)=2.849, 95% CI(0.546, 3.054), p = 0.005] and the APc group [mean = 1.877 kg, t(72)=2.688, 95% CI(0.485, 3.268), p = 0.009] showed significant weight gain. Patients taking clozapine, olanzapine or quetiapine showed significant weight gain compared to those not taking these medications [mean difference=1.707 kg, t(271)= 2.061, 95% CI(0.077, 3.337), p = 0.040)]. CONCLUSION: Patients receiving APs and APs with other psychotropics gain weight during long-term treatment. It is possible that weight gain is mainly driven by APs.

Anticipating manic and depressive transitions in patients with bipolar disorder using early warning signals.

BACKGROUND: In bipolar disorder treatment, accurate episode prediction is paramount but remains difficult. A novel idiographic approach to prediction is to monitor generic early warning signals (EWS), which may manifest in symptom dynamics. EWS could thus form personalized alerts in clinical care. The present study investigated whether EWS can anticipate manic and depressive transitions in individual patients with bipolar disorder. METHODS: Twenty bipolar type I/II patients (with ≥ 2 episodes in the previous year) participated in ecological momentary assessment (EMA), completing five questionnaires a day for four months (Mean = 491 observations per person). Transitions were determined by weekly completed questionnaires on depressive (Quick Inventory for Depressive Symptomatology Self-Report) and manic (Altman Self-Rating Mania Scale) symptoms. EWS (rises in autocorrelation at lag-1 and standard deviation) were calculated in moving windows over 17 affective and symptomatic EMA states. Positive and negative predictive values were calculated to determine clinical utility. RESULTS: Eleven patients reported 1-2 transitions. The presence of EWS increased the probability of impending depressive and manic transitions from 32-36% to 46-48% (autocorrelation) and 29-41% (standard deviation). However, the absence of EWS could not be taken as a sign that no transition would occur in the near future. The momentary states that indicated nearby transitions most accurately (predictive values: 65-100%) were full of ideas, worry, and agitation. Large individual differences in the utility of EWS were found. CONCLUSIONS: EWS show theoretical promise in anticipating manic and depressive transitions in bipolar disorder, but the level of false positives and negatives, as well as the heterogeneity within and between individuals and preprocessing methods currently limit clinical utility.

Impact of coping styles on substance use in persons with psychosis, siblings, and controls.

BACKGROUND: Substance use is overrepresented in patients with psychosis. Maladaptive coping has been proposed as one of the mechanisms which might underlie this high prevalence. Patients are known to apply more maladaptive coping compared to the healthy population. However, it is unknown whether coping is associated with the use of different substances across those with different vulnerability for psychosis, and whether coping mediates the possible association between life events and substance use. METHODS: In this multicenter, cohort study, 429 patients, 504 siblings, and 220 controls were included. We determined whether coping was associated with tobacco smoking, cannabis use, or alcohol consumption. Multivariable logistic regression models were applied whilst correcting for potential confounders. We performed post-hoc analyses to explore the association between negative life events, tobacco smoking, and the role of coping as a mediator in patients with psychosis. RESULTS: A positive association was found in patients between passive coping and tobacco smoking (fully adjusted OR 1.65, 95% CI 1.18-2.31). Tobacco smoking patients experienced more negative life events compared to non-smoking patients and passive coping mediated this association. In siblings and controls, none of the coping strategies were associated with substance use. CONCLUSIONS: The coping style of patients with psychosis is associated with tobacco smoking and mediates the association between negative events and tobacco smoking. No significant associations were found in siblings, controls or concerning other substance use. Future research is required to examine whether enhancing healthy coping strategies decreases tobacco use in patients with psychosis.

Comparing psychotic experiences in low-and-middle-income-countries and high-income-countries with a focus on measurement invariance.

BACKGROUND: The prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias. METHODS: A community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses. RESULTS: MI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = -0.42) and underestimation (e.g. magical thinking, d = -0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition. CONCLUSION: Previous studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.